Avermectin B1b is a natural macrocyclic lactone antiparasitic/insecticide produced by Streptomyces avermitilis. Avermectin B1b can induce cytotoxicity, apoptosis, and autophagy. Avermectin B1b can be used in research related to antiparasitic therapy, agricultural pest control, and cancer treatment[1-4].
In vitro, Avermectin B1b combined with Avermectin B1a mixture (3μM; ratio 1:4) was applied to chikungunya virus (CHIKV)-infected BHK-21 cells for 14–18h. The Avermectin B1b and Avermectin B1a mixture significantly inhibited viral positive- and negative-strand RNA synthesis, downregulated nsP1, nsP3, and E2 protein expression, and reduced infectious viral particle production[5]. Avermectin B1b combined with Avermectin B1a mixture (4.194–6.506μM; ratio 1:4) was applied to MNNG, MG63, and U2OS human osteosarcoma cells for 48h. The Avermectin B1b and Avermectin B1a mixture inhibited cell proliferation and colony formation, impaired migration and invasion abilities, induced G1 phase arrest and apoptosis, and activated the AMPK/ULK1 signaling pathway to promote autophagy (elevated LC3B-II/I ratio, upregulation of ATG7, ATG13, ATG14, Beclin1)[6].
In vivo, Avermectin B1b combined with Avermectin B1a mixture (5mg/kg; ratio 1:4; once daily) was orally administered to male Balb/c nu/nu nude mice bearing subcutaneous xenografts of LA795 lung adenocarcinoma cells for 4 consecutive weeks. The Avermectin B1b and Avermectin B1a mixture significantly inhibited tumor growth and reduced tumor volume and weight[7]. Avermectin B1b combined with Avermectin B1a mixture (2mg/kg; ratio 1:4; single dose) was orally administered to lipopolysaccharide-induced acute lung injury model BALB/C mice (administered 1h before intranasal LPS at 0.5mg/kg). The Avermectin B1b and Avermectin B1a mixture significantly reduced TNF-α and IL-6 levels in bronchoalveolar lavage fluid, decreased total cell counts, neutrophil and macrophage infiltration in bronchoalveolar lavage fluid, lowered lung wet/dry ratio and myeloperoxidase activity, alleviated pathological changes including alveolar wall thickening, alveolar hemorrhage, and interstitial edema, inhibited p38MAPK and ERK phosphorylation and IκB degradation, and blocked MAPK and NF-κB pathway activation[8].
References:
[1] Siddique S, Ashraf Qureshi F. Kinetics of Avermectin B1b Production by Streptomyces avermitilis 41445 UV 45(m)3 in Shake Flask Culture. Iran J Biotechnol. 2020 Jul 1;18(3):e2356.
[2] El-Marzoky AM, Ali MAMS, Elnahal ASM, et al. The Combination Effect of Purpureocillium lilacinum Strain (AUMC 10620) and Avermectin (B1a and B1b) on Control Citrus Nematode Tylenchulus semipenetrans (Cobb) Under Laboratory and Field Conditions. Biology (Basel). 2025 Jan 13;14(1):60.
[3] Siddique S, Syed Q, Adnan A, et al. Production and Screening of High Yield Avermectin B1b Mutant of Streptomyces avermitilis 41445 Through Mutagenesis. Jundishapur J Microbiol. 2014 Feb;7(2):e8626.
[4] Korystov YN, Ermakova NV, Kublik LN, et al. Avermectins inhibit multidrug resistance of tumor cells. Eur J Pharmacol. 2004 Jun 16;493(1-3):57-64.
[5] Varghese FS, Kaukinen P, Gläsker S, et al. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antiviral Res. 2016 Feb;126:117-24.
[6] Fei X, Li Z, Pan Z, et al. Avermectin B1 mediates antitumor activity and induces autophagy in osteosarcoma through the AMPK/ULK1 signaling pathway. Cancer Chemother Pharmacol. 2024 Oct;94(4):599-613.
[7] Zhang X, Zhang G, Zhai W, et al. Inhibition of TMEM16A Ca2+-activated Cl- channels by avermectins is essential for their anticancer effects. Pharmacol Res. 2020 Jun;156:104763.
[8] Zhang X, Li J, Chen C, et al. Protective effect of abamectin on acute lung injury induced by lipopolysaccharide in mice. Fundam Clin Pharmacol. 2011 Dec;25(6):700-7.